We have profiled circulating cell-free miRNAs in the plasma from 5 HCV infected individuals prior to and after their development of hepatocellular carcinoma (HCC). This is a collaborative study performed with Dr. Stephen Feinstone of the Food and Drug Administration (FDA) and Dr. Ajit Kumar of George Washington University. Dr. Feinstone has a set of paired plasma panels from 50 patients with chronic HCV infections. These are from Japanese patients who have been followed every 2 months with ultrasound and alpha fetal protein determinations to screen for development of hepatocellular cancer (HCC). The patients have been followed prospectively for many years, from before they developed HCC to after they developed the cancer. We employed 5 samples that were obtained two years before HCC was detected and compared these to 5 plasma samples of the same individuals after they were diagnosed with HCC. Sequential plasmas from these patients have been stored; so many temporal changes circulating microRNA results can be confirmed and monitored with additional plasma samples. Our profiling results are encouraging that this approach could yield useful biomarkers for monitoring HCV disease progression.